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Nuclear Dynamic, Organization and Genome Stability

Nuclear Dynamic, Organization and Genome Stability

Objective

The eukaryotic genome is packaged into large-scale chromatin structures occupying distinct domains in the cell nucleus. Nuclear compartmentalization has recently been proposed to play an important role in genome stability but the molecular steps regulated remain to be defined. Focusing on Double strand breaks (DSBs) in response to which cells activate checkpoint and DNA repair pathways, we propose to characterize the spatial and temporal behavior of damaged chromatin and determine how this affects the maintenance of genome integrity. Currently, most studies concerning DSBs signaling and repair have been realized on asynchronous cell populations, which makes it difficult to precisely define the kinetics of events that occur at the cellular level. We thus propose to follow the nuclear localization and dynamics of an inducible DSB concomitantly with the kinetics of checkpoint activation and DNA repair at a single cell level and along the cell cycle. This will be performed using budding yeast as a model system enabling the combination of genetics, molecular biology and advanced live microscopy. We recently demonstrated that DSBs relocated to the nuclear periphery where they contact nuclear pores. This change in localization possibly regulates the choice of the repair pathway through steps that are controlled by post-translational modifications. This proposal aims at dissecting the molecular pathways defining the position of DSBs in the nucleus by performing genetic and proteomic screens, testing the functional consequence of nuclear position for checkpoint activation and DNA repair by driving the DSB to specific nuclear landmarks and, defining the dynamics of DNA damages in different repair contexts. Our project will identify new players in the DNA repair and checkpoint pathways and further our understanding of how the compartmentalization of damaged chromatin into the nucleus regulates these processes to insure the transmission of a stable genome.

Principal Investigator

Karine Marie Renée Dubrana (Dr.)

Host institution

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

Address

Rue Leblanc 25
75015 Paris 15

France

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 499 863

Principal Investigator

Karine Marie Renée Dubrana (Dr.)

Administrative Contact

Olivier Leroy (Mr.)

Beneficiaries (1)

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COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

France

EU Contribution

€ 1 499 863

Project information

Grant agreement ID: 281287

Status

Closed project

  • Start date

    1 February 2012

  • End date

    31 January 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 499 863

  • EU contribution

    € 1 499 863

Hosted by:

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

France